The purpose of the proposed research is to determine the central neuroanatomical substrates mediating antagonistic alpha- and beta-adrenergic influences on feeding behavior and the role of these adrenergic systems in the physiological control of naturally motivated feeding behavior. By the use of localized central injections of alpha- and beta-adrenergic agonists, the principal investigator has recently obtained evidence to suggest that alpha- and beta-receptor systems, which respectively stimulate and suppress feeding behavior, may be anatomically differentiated and highly localized within the ventral diencephalon of the rat. Independently, recent histofluorescence studies have identified two adrenergic pathways which selectively innervate the very diencephalic regions which the principal investigator found to be maximally and selectively sensitive to alpha or beta stimulation. The proposed research will use intracranial drug injections and lesion techniques to: 1) determine whether amphetamine or other catecholamine-releasing drugs can produce, through endogenous norepinephrine release, the same localized pattern of feeding effects obtained with exogenous alpha- and beta- adrenergic stimulation of the diencephalon; 2) study the specific norepinephrine pathways that innervate the diencephalon, in terms of their function in the regulation of natural feeding behavior; and 3) examine the functional relationship between the different norepinephrine pathways innervating specific diencephalic regions and the alpha- and beta-receptor feeding systems localized in these regions. The proposed research has direct bearing on the neurochemical action of drugs, such as amphetamine, which may be used therapeutically in the treatment of feeding pathologies such as obesity and anorexia nervosa. BIBLIOGRAPHIC REFERENCES: Leibowitz, S.F. Identification of catecholamine receptor mechanisms in the perifornical lateral hypothalamus and their role in mediating amphetamine and l-DOPA anorexia. In: Central Mechanisms of Anorectic Drugs (S. Garattini, editor). Raven Press, New York, 1977, in press. Leibowitz, S.F. Histamine: Modification of behavioral and physiological parameters of body fluid homeostasis. In: Histamine Receptors (T.O. Yellin, editor). Spectrum Publications, New York, 1977, in press.